DSM265   Click here for help

GtoPdb Ligand ID: 9644

PDB Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: DSM265 is an optimised candidate and clinical lead from the triazolopyrimidine structural class and represents a new class of antimalarial drug [1].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 55.11
Molecular weight 415.07
XLogP 4.9
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES Cc1cc(Nc2ccc(cc2)S(F)(F)(F)(F)F)n2c(n1)nc(n2)C(F)(F)C
Isomeric SMILES Cc1cc(Nc2ccc(cc2)S(F)(F)(F)(F)F)n2c(n1)nc(n2)C(F)(F)C
InChI InChI=1S/C14H12F7N5S/c1-8-7-11(26-13(22-8)24-12(25-26)14(2,15)16)23-9-3-5-10(6-4-9)27(17,18,19,20)21/h3-7,23H,1-2H3
InChI Key OIZSVTOIBNSVOS-UHFFFAOYSA-N
References
1. Coteron JM, Marco M, Esquivias J, Deng X, White KL, White J, Koltun M, El Mazouni F, Kokkonda S, Katneni K et al.. (2011)
Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential.
J Med Chem, 54 (15): 5540-61. [PMID:21696174]
2. Kokkonda S, Deng X, White KL, El Mazouni F, White J, Shackleford DM, Katneni K, Chiu FCK, Barker H, McLaren J et al.. (2020)
Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria.
J Med Chem, 63 (9): 4929-4956. [PMID:32248693]
3. Llanos-Cuentas A, Casapia M, Chuquiyauri R, Hinojosa JC, Kerr N, Rosario M, Toovey S, Arch RH, Phillips MA, Rozenberg FD et al.. (2018)
Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study.
Lancet Infect Dis, 18 (8): 874-883. [PMID:29909069]
4. McCarthy JS, Lotharius J, Rückle T, Chalon S, Phillips MA, Elliott S, Sekuloski S, Griffin P, Ng CL, Fidock DA et al.. (2017)
Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study.
Lancet Infect Dis, 17 (6): 626-635. [PMID:28363636]
5. Phillips MA, Lotharius J, Marsh K, White J, Dayan A, White KL, Njoroge JW, El Mazouni F, Lao Y, Kokkonda S et al.. (2015)
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.
Sci Transl Med, 7 (296): 296ra111. [PMID:26180101]
6. Sulyok M, Rückle T, Roth A, Mürbeth RE, Chalon S, Kerr N, Samec SS, Gobeau N, Calle CL, Ibáñez J et al.. (2017)
DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection.
Lancet Infect Dis, 17 (6): 636-644. [PMID:28363637]